Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale “off-context” gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature–guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors.

This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests different therapeutic approaches according to the subgroup profile.

The esophagus traverses three body compartments (neck, thorax, and abdomen) and is surrounded at each level by vital organs. Injuries to the esophagus may be classified as foreign body ingestion, caustic ingestion, esophageal perforation, and esophageal trauma. These lesions can be life-threatening either by digestive contamination of surrounding structures in case of esophageal wall breach or concomitant damage of surrounding organs. Early diagnosis and timely therapeutic intervention are the keys of successful management.

Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT.Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3 4.4 (mean SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4 4.3 kg . m 2 , weight was 87.9 16.6% of ideal body weight (IBW).Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): I: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI $60% (27%); III: weight $90% IBW and CHI <60% (17%); IV: weight $90% IBW and CHI $60% (28%). Overall, 72% were depleted corresponding to groups I, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups I, II, III whereas IPF were concentrated in group III. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III.To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant. Eur Respir J 2000; 16: 1050±1055.

Pleuro-pulmonary solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal neoplasm of uncertain histogenesis, unknown molecular features, and unpredictable clinical behavior. Although complete resection is universally accepted as the most important single prognostic factor, some clinicopathologic characteristics (gross appearance, tumor size, mitotic index, tumor necrosis, hypercellularity, and pleomorphism) are related to patient outcome, and a staging system based on these parameters with practical therapeutical implications has been recently proposed by de Perrot et al. Here, 88 pleuro-pulmonary SFTs were collected and clinicopathologic characteristics including de Perrot classification, patients' follow-up, p53 expression, and several "targetable" kinases [c-kit, v-raf murine sarcoma viral oncogene homolog B1, platelet-derived growth factor receptor (PDGFR)-alpha/beta, c-met, epidermal growth factor receptor (EGFR)] were retrospectively analyzed. Fifty-two cases (59%) had at least 1 clinicopathologic feature related to malignancy, whereas mortality and recurrences occurred in 10.2% and 18.2% of the cases, respectively. de Perrot staging and high p53 expression were significantly related to the conventional clinicopathologic prognostic features as well as to overall survival (OS) and disease-free survival (DFS) (P<0.001). At multivariate analysis, high p53 expression and tumor necrosis were the only parameters significantly associated with OS and DFS (P=0.017 and P=0.012, respectively). Immunohistochemical expression was frequently detected for PDGFR-alpha (97.7%), PDGFR-beta (86.5%), and hepatocyte growth factor receptor (96.6%), whereas missense mutations were only identified in 2 cases both involving PDGFR-beta (exons 18 and 20). We conclude that de Perrot stratification of SFT is a reliable prognostic indicator and merits consideration in view of its suggestions for the management of these tumors in daily practice. p53 expression may represent a valid and easy-to-test prognostic factor significantly related to OS and DFS. Although mutations of the corresponding genes are rare events in SFT, PDGFR-alpha/beta, and hepatocyte growth factor receptor tyrosine kinases should be further investigated given the availability of specific inhibitory molecules which might provide useful and novel therapeutical approaches for SFT patients.

No abstract

No abstract

The new allocation system aimed at lowering mortality on the RWL, but also offered an access to LTx for new patients with end-stage respiratory failure. The HEWL increased the likelihood of mortality after LTx, but permitted acceptable mid-term survival rates. The high mortality associated with the use of ECMO should be interpreted cautiously.